Small interfering RNA (siRNA) is a short, double-stranded nucleic acid molecule that can be used for post-transcriptional gene silencing. In theory, siRNA can be used to suppress the expression of e.g., cancer-related genes by silencing specific complementary mRNA associated with those genes and down-regulating expression of the associated gene products, e.g., proteins. It would be advantageous to co-administer siRNA, for the silencing of cancer related genes, with small molecule cancer drugs to more effectively treat cancer.
In practice, however, the therapeutic application of siRNA technology has been limited because siRNA is difficult to effectively deliver to the site of its action in a subject. Naked siRNA is water soluble, readily degraded by endogenous enzymes and generally too large and negatively charged to cross cell membranes by diffusion, a mechanism by which small molecule drugs generally enter cells.
Many small molecule drugs are also difficult to administer to a subject, but for different reasons. Many small molecule cancer drugs have poor aqueous solubility and, e.g., for intravenous (IV) administration, require large volumes of an aqueous vehicle. Alternatively, a more direct administration (e.g., subcutaneous delivery) of many small molecule cancer drugs can result in local toxicity and low levels of activity. Thus, there is a need for more efficient and effective delivery to subjects of both siRNA and small molecule chemotherapeutic agents.